Hematopathology

Hematopathology US Medical PG Question 1: A 45-year-old woman comes to the physician because of a 1-week history of fatigue and bruises on her elbows. Examination shows a soft, nontender abdomen with no organomegaly. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Serum electrolyte concentrations are within normal limits. A bone marrow biopsy is most likely to show which of the following findings?

• A. Increased myeloblast count
• B. Sheets of abnormal plasma cells
• C. Wrinkled cells with a fibrillary cytoplasm
• D. Hypocellular bone marrow (Correct Answer)
• E. Dysplastic bone with ringed sideroblasts

Hematopathology Explanation: ***Hypocellular bone marrow*** - The patient presents with **pancytopenia** (low hemoglobin, leukocytes, and platelets) and a very low **reticulocyte count**, indicating severely impaired hematopoiesis [1]. - This constellation of findings, in the absence of organomegaly or other specific features, strongly suggests **aplastic anemia**, which is characterized by a **hypocellular bone marrow** with significant reduction in hematopoietic cells and replacement by fat [1][3]. *Increased myeloblast count* - An increased **myeloblast count** in the bone marrow is characteristic of **acute myeloid leukemia (AML)**. - While pancytopenia can occur in AML, the distinguishing feature would be a high percentage of blasts (typically >20%) in the bone marrow, which is not implied by the general presentation [1]. *Sheets of abnormal plasma cells* - **Sheets of abnormal plasma cells** are the hallmark of **multiple myeloma** [2]. - This condition primarily presents with bone pain, hypercalemia, renal failure, and anemia, but not typically with severe pancytopenia and bruising as the primary presenting symptoms without other myeloma-defining events [2]. *Wrinkled cells with a fibrillary cytoplasm* - **Wrinkled cells with a fibrillary cytoplasm** (Gaucher cells) are pathognomonic for **Gaucher disease**, a lysosomal storage disorder. - Gaucher disease typically presents with hepatosplenomegaly, bone crises, and neurological symptoms, not primarily with aplastic anemia. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Red Blood Cell and Bleeding Disorders, pp. 662-663. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 617-618. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 595-596.

Hematopathology US Medical PG Question 2: A 24-year-old woman complains of intermittent fever and joint pain. She says that these symptoms have been present for the past month. Before that, she had no signs or symptoms and was completely healthy. She has also lost her appetite and some weight. A complete blood count (CBC) showed severe pancytopenia. What is the next best step in evaluating this patient?

• A. Repeated CBCs for several weeks and reassess
• B. Treatment with corticosteroids
• C. Treatment with antibiotics
• D. Treatment for acute leukemia
• E. Bone marrow examination (Correct Answer)

Hematopathology Explanation: ***Bone marrow examination*** - The combination of **fever**, **joint pain**, **weight loss**, and **pancytopenia** in a previously healthy young woman raises suspicion for serious hematologic conditions like **aplastic anemia** or **acute leukemia**. - A **bone marrow examination** is crucial for definitive diagnosis by evaluating the cellularity, morphology, and presence of abnormal cells. *Repeated CBCs for several weeks and reassess* - This approach is inappropriate given the **severe pancytopenia** and progressive symptoms, which indicate an urgent underlying pathology. - Delaying diagnosis could worsen the patient's condition and compromise treatment outcomes due to the potential for severe infections or bleeding. *Treatment with corticosteroids* - While corticosteroids might be used in some autoimmune conditions causing pancytopenia, initiating treatment without a definitive diagnosis is premature and could mask the underlying cause, especially in cases of malignancy. - There is no specific indication for corticosteroid use in this scenario without further diagnostic information. *Treatment with antibiotics* - Although **fever** is present, there's no clear evidence of an infection (like localized symptoms or positive cultures), and **pancytopenia** is not primarily managed with antibiotics. - Administering antibiotics empirically without a confirmed infection addresses a symptom rather than the underlying progressive hematological disorder. *Treatment for acute leukemia* - While **acute leukemia** is a strong possibility, definitive treatment should only commence after a confirmed diagnosis through **bone marrow examination**, as misdiagnosis can lead to inappropriate and harmful therapy. - Other conditions like severe aplastic anemia also present with similar features but require different management strategies.

Hematopathology US Medical PG Question 3: A 63-year-old man comes to the physician because of increasing generalized fatigue for 3 months. He is having more difficulty with keeping up with his activities of daily living and has lost 2.5 kg (5.5 lb) over the past month. He has hypertension and hyperlipidemia. He does not smoke and drinks two to three beers on weekends. His medications include lisinopril, hydrochlorothiazide, and atorvastatin. His temperature is 37.1°C (98.8°F), pulse is 85/min, respirations are 15/min, and blood pressure is 125/73 mm Hg. Examination shows pale conjunctivae. The remainder of the examination shows no abnormalities. His hematocrit is 27.3%, leukocyte count is 4500/mm3, and platelet count is 102,000/mm3. A peripheral blood smear shows numerous blast cells that stain positive for myeloperoxidase, CD33, and CD34. Which of the following is the most likely diagnosis?

• A. Non-Hodgkin lymphoma
• B. Acute myeloid leukemia (Correct Answer)
• C. Hairy cell leukemia
• D. Chronic lymphocytic leukemia
• E. Acute lymphoblastic leukemia

Hematopathology Explanation: ***Acute myeloid leukemia*** - The presence of **numerous blast cells** that stain positive for **myeloperoxidase (MPO)** and **CD33** is highly characteristic of **acute myeloid leukemia (AML)**. - The patient's symptoms of **fatigue**, **weight loss**, **pale conjunctivae (anemia)**, and **pancytopenia** (low hematocrit, leukopenia, thrombocytopenia) are consistent with bone marrow infiltration by leukemic blasts. *Non-Hodgkin lymphoma* - Characterized by **lymphadenopathy** and systemic 'B' symptoms (fever, night sweats, weight loss), which are not prominent features here. - While it can cause cytopenias, the presence of **myeloperoxidase-positive blasts** would point away from lymphoma, which involves lymphocytes. *Hairy cell leukemia* - Typically presents with **pancytopenia**, **splenomegaly**, and characteristic **hairy cells** on peripheral smear. - These cells are **CD103, CD123, and CD25 positive** and tartrate-resistant acid phosphatase (TRAP) positive, which differs from the findings in this case. *Chronic lymphocytic leukemia* - Characterized by an accumulation of **mature-appearing lymphocytes** (not blasts) in the blood, bone marrow, and lymph nodes. - These cells typically express **CD5 and CD20**, and **myeloperoxidase** would be negative. *Acute lymphoblastic leukemia* - Involves **lymphoblasts**, which are typically **MPO-negative** and express lymphoid markers like **CD10, CD19, and CD22**. - While it can present with similar symptoms and pancytopenia as AML, the **MPO positivity rules it out**.

Hematopathology US Medical PG Question 4: A 64-year-old woman comes to the physician because of a 7-month history of abdominal discomfort, fatigue, and a 6.8-kg (15-lb) weight loss. Physical examination shows generalized pallor and splenomegaly. Laboratory studies show anemia with pronounced leukocytosis and thrombocytosis. Cytogenetic analysis shows a BCR-ABL fusion gene. A drug with which of the following mechanisms of action is most appropriate for this patient?

• A. Ribonucleotide reductase inhibitor
• B. Monoclonal anti-HER-2 antibody
• C. Topoisomerase II inhibitor
• D. Monoclonal anti-CD20 antibody
• E. Tyrosine kinase inhibitor (Correct Answer)

Hematopathology Explanation: ***Tyrosine kinase inhibitor*** - The patient's symptoms (abdominal discomfort, fatigue, weight loss, pallor, splenomegaly), laboratory findings (**anemia with pronounced leukocytosis and thrombocytosis**), and the presence of a **BCR-ABL fusion gene** are highly characteristic of **Chronic Myeloid Leukemia (CML)**. - The **BCR-ABL fusion gene** encodes a constitutively active **tyrosine kinase**, which is the hallmark of CML and the primary therapeutic target for **tyrosine kinase inhibitors (TKIs)** like imatinib. *Ribonucleotide reductase inhibitor* - **Ribonucleotide reductase inhibitors** (e.g., hydroxyurea) block DNA synthesis and are used in myeloproliferative disorders to reduce cell counts, but they are not specific to the **BCR-ABL fusion gene** and are not the most appropriate first-line targeted therapy for CML. - While they can control symptoms, they do not target the underlying molecular defect in CML as effectively as TKIs. *Monoclonal anti-HER-2 antibody* - **Monoclonal anti-HER-2 antibodies** (e.g., trastuzumab) are used to treat **HER-2 positive breast cancer** and some gastric cancers. - They are not relevant to the treatment of CML, which is characterized by the **BCR-ABL fusion gene**. *Topoisomerase II inhibitor* - **Topoisomerase II inhibitors** (e.g., etoposide, doxorubicin) prevent DNA unwinding and replication, leading to cell death, and are used in various hematologic malignancies and solid tumors. - These drugs are broad-spectrum chemotherapeutic agents not specifically targeted to the **BCR-ABL fusion protein** in CML and are not first-line therapy for this condition. *Monoclonal anti-CD20 antibody* - **Monoclonal anti-CD20 antibodies** (e.g., rituximab) target the CD20 protein on B lymphocytes and are primarily used to treat **B-cell non-Hodgkin lymphoma** and some autoimmune diseases. - They have no role in the direct treatment of CML, which is a myeloid malignancy.

Hematopathology US Medical PG Question 5: A 67-year-old man comes to the physician because of a 2-month history of generalized fatigue. On examination, he appears pale. He also has multiple pinpoint, red, nonblanching spots on his extremities. His spleen is significantly enlarged. Laboratory studies show a hemoglobin concentration of 8.3 g/dL, a leukocyte count of 81,000/mm3, and a platelet count of 35,600/mm3. A peripheral blood smear shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic inclusions. Which of the following is the most likely diagnosis?

• A. Acute lymphoblastic leukemia
• B. Myelodysplastic syndrome
• C. Hairy cell leukemia
• D. Acute myelogenous leukemia (Correct Answer)
• E. Chronic myelogenous leukemia

Hematopathology Explanation: ***Acute myelogenous leukemia*** - The presence of immature cells with **large, prominent nucleoli** and **pink, elongated, needle-shaped cytoplasmic inclusions** (**Auer rods**) on peripheral blood smear is pathognomonic for **acute myeloid leukemia (AML)**. - The pancytopenia (anemia, thrombocytopenia) and extreme leukocytosis, along with generalized fatigue and pale appearance, are consistent with the presentation of AML. *Acute lymphoblastic leukemia* - Characterized by the proliferation of **lymphoblasts** (immature lymphocytes) in the bone marrow and peripheral blood, which typically lack Auer rods. - While it can present with fatigue, pallor, and cytopenias, the specific morphologic features of the blast cells are different. *Myelodysplastic syndrome* - Involves ineffective hematopoiesis leading to **cytopenias** and dysplastic features in mature blood cells, but typically features less aggressive proliferation of immature cells than acute leukemias and **lacks Auer rods**. - While it can progress to AML, the current description points to actively proliferating immature cells. *Hairy cell leukemia* - Characterized by **B lymphocytes with cytoplasmic projections** ("hairy cells") and is typically associated with **massive splenomegaly** and **pancytopenia**, but the characteristic Auer rods are absent. - The cell morphology described (large nucleoli, needle-shaped inclusions) is inconsistent with hairy cells. *Chronic myelogenous leukemia* - Characterized by the **Philadelphia chromosome (BCR-ABL1 fusion gene)** and a marked increase in mature and immature myeloid cells, including granulocytes at various stages of maturation, but typically **lacks Auer rods** and usually has a higher proportion of mature rather than acutely immature cells. - While it presents with leukocytosis and splenomegaly, the prominent immature cells with nucleoli and Auer rods are not features of CML.

Hematopathology US Medical PG Question 6: A 5-year-old patient presents to the pediatrician's office with fatigue and swollen lymph nodes. Extensive work-up reveals a diagnosis of acute lymphoblastic leukemia. In an effort to better tailor the patient's treatments, thousands of genes are arranged on a chip and a probe is made from the patient's mRNA (converted to cDNA). This probe is then hybridized to the chip in order to measure the gene expression of thousands of genes. The technology used to investigate this patient's gene expression profile is best for detecting which of the following types of genetic abnormalities?

• A. Trisomies
• B. Large scale chromosomal deletions
• C. Frame-shift mutations
• D. Chromosomal translocations (Correct Answer)
• E. Single nucleotide polymorphisms

Hematopathology Explanation: ***Chromosomal translocations*** - The described process, involving gene expression analysis using a **DNA chip** (microarray), is effective at identifying translocations indirectly by detecting abnormal **fusion transcripts** or altered **gene expression patterns** resulting from the translocation. - Many leukemias, especially **acute lymphoblastic leukemia (ALL)**, are characterized by specific chromosomal translocations that lead to the creation of **oncogenic fusion genes**, thereby altering gene expression. *Trisomies* - Trisomies are **numerical chromosomal abnormalities** involving an extra copy of an entire chromosome, which are typically detected by **karyotyping** or **fluorescence in situ hybridization (FISH)**, not by gene expression arrays directly unless they cause a widespread, quantifiable change in dosage. - While gene expression might be altered, a microarray designed for gene expression profiling is not the primary or most sensitive tool for identifying the presence of an entire extra chromosome. *Large scale chromosomal deletions* - Large-scale deletions would lead to a **reduced expression** of a large number of genes in the affected region, but direct detection of the deletion itself is usually done with **comparative genomic hybridization (CGH)** or **karyotyping**, which are designed to identify copy number variations. - While gene chips can show altered expression, they are less precise for delineating the exact boundaries of a deletion compared to genetic-level analyses. *Frame-shift mutations* - **Frame-shift mutations** are small insertions or deletions within a gene that alter the reading frame, leading to a truncated or non-functional protein. - These are typically detected by **DNA sequencing**, not broadly by gene expression microarrays, which measure the abundance of mRNA transcripts rather than sequence changes. *Single nucleotide polymorphisms* - **Single nucleotide polymorphisms (SNPs)** are variations in a single nucleotide at a specific position in the genome. - While specialized SNP arrays exist, general gene expression microarrays are designed to quantify mRNA levels and are not the primary method for identifying individual SNPs, which require **genotyping** techniques.

Hematopathology US Medical PG Question 7: A 5-year-old male is brought to his pediatrician after recurrent, prolonged upper respiratory infections over a period of several months. Physical exam reveals petechiae on the patient's legs and arms. Laboratory studies show hemoglobin: 10 g/dL, platelet count: 35,000/mm^3, leukocyte count: 6,600/mm^3. A bone marrow aspiration shows an abundance of lymphoblasts indicative of acute lymphoblastic leukemia (ALL). Positive immunostaining for which of the following would support a diagnosis of precursor B-cell leukemia?

• A. CD2, CD8
• B. TdT, HER-2
• C. CD4, CD5
• D. CD19, CD10 (Correct Answer)
• E. CD30, CD15

Hematopathology Explanation: ***CD19, CD10*** - **CD19** is a pan B-cell marker, expressed on almost all B-lymphocytes from early pre-B-cells through mature B-cells. Its presence, along with **CD10**, is highly characteristic of **precursor B-cell ALL (B-ALL)**. - **CD10**, also known as common acute lymphoblastic leukemia antigen (CALLA), is typically expressed on **early B-cell progenitors** and is a reliable marker for differentiating B-ALL from other leukemias. *CD2, CD8* - **CD2** and **CD8** are markers primarily associated with **T-lymphocytes**. While CD2 is a pan T-cell marker, CD8 identifies cytotoxic T cells. - Their positivity would suggest a **T-cell ALL (T-ALL)**, not the precursor B-cell type indicated by the clinical scenario. *TdT, HER-2* - **Terminal deoxynucleotidyl transferase (TdT)** is an enzyme found in immature lymphocytes (both B and T cells) and is positive in most ALL cases, but it is not specific for B-cell lineage. - **HER-2** is an oncogene and a growth factor receptor overexpressed in certain solid tumors (especially breast cancer) but is not a marker used for leukemia classification. *CD4, CD5* - **CD4** is a marker for helper T cells, while **CD5** is expressed on a subset of T cells and some B-cell malignancies (e.g., chronic lymphocytic leukemia/small lymphocytic lymphoma). - These markers are primarily associated with **T-cell lineages** and would not support a diagnosis of precursor B-cell leukemia in this context. *CD30, CD15* - **CD30** and **CD15** are classical markers for **Hodgkin lymphoma** (specifically the classical type). - Their presence would point towards a lymphoproliferative disorder different from acute lymphoblastic leukemia.

Hematopathology US Medical PG Question 8: A 72-year-old man goes to his primary care provider for a checkup after some blood work showed lymphocytosis 3 months ago. He says he has been feeling a bit more tired lately but doesn’t complain of any other symptoms. Past medical history is significant for hypertension and hyperlipidemia. He takes lisinopril, hydrochlorothiazide, and atorvastatin. Additionally, his right hip was replaced three years ago due to osteoarthritis. Family history is noncontributory. He drinks socially and does not smoke. Today, he has a heart rate of 95/min, respiratory rate of 17/min, blood pressure of 135/85 mm Hg, and temperature of 36.8°C (98.2°F). On physical exam, he looks well. His heartbeat has a regular rate and rhythm and lungs that are clear to auscultation bilaterally. Additionally, he has mild lymphadenopathy of his cervical lymph nodes. A complete blood count with differential shows the following: Leukocyte count 5,000/mm3 Red blood cell count 3.1 million/mm3 Hemoglobin 11.0 g/dL MCV 95 um3 MCH 29 pg/cell Platelet count 150,000/mm3 Neutrophils 40% Lymphocytes 40% Monocytes 5% A specimen is sent for flow cytometry that shows a population that is CD 5, 19, 20, 23 positive. Which of the following is the most likely diagnosis?

• A. Chronic lymphocytic leukemia (Correct Answer)
• B. Immune thrombocytopenic purpura
• C. Aplastic anemia
• D. Acute lymphoblastic leukemia
• E. Tuberculosis

Hematopathology Explanation: ***Chronic lymphocytic leukemia*** - The patient presents with mild **lymphadenopathy**, a **history of lymphocytosis**, and a **flow cytometry** showing cells positive for **CD5, CD19, CD20, and CD23**, which is pathognomonic for **CLL**. - While the total leukocyte count is within normal limits due to the absolute neutrophil decrease, the persistent lymphocytosis and characteristic immunophenotype are highly indicative of CLL. *Immune thrombocytopenic purpura* - This condition is characterized by **isolated thrombocytopenia** caused by autoantibody-mediated platelet destruction, which is not supported by the patient's normal platelet count (150,000/mm3). - While it can cause fatigue, it doesn't explain the lymphocytosis or the specific **CD marker profile**. *Aplastic anemia* - Aplastic anemia involves **pancytopenia** (decreased red blood cells, white blood cells, and platelets) due to bone marrow failure, which is not consistent with the patient's normal-range leukocyte and platelet counts. - The patient's presentation with lymphocytosis and lymphadenopathy further makes this diagnosis unlikely. *Acute lymphoblastic leukemia* - **ALL** typically presents with symptoms related to **bone marrow failure** (anemia, thrombocytopenia, infections) and often very **high blast counts** in the peripheral blood and bone marrow. - While it involves lymphocytes, the specific **CD5/19/20/23 co-expression** is characteristic of CLL, and ALL usually involves more aggressive symptoms and a different immunophenotype. *Tuberculosis* - **Tuberculosis** is an infectious disease that can cause **lymphadenopathy** and systemic symptoms like fatigue, but it is typically associated with a **caseating granulomatous inflammation** and is diagnosed via cultures or PCR rather than flow cytometry. - It would not explain the specific **B-cell lymphocytosis** with the described immunophenotype.

Hematopathology US Medical PG Question 9: A 27-year-old woman presents to the emergency department complaining of a left-sided headache and right-sided blurry vision. She states that 2 weeks ago she developed dark urine and abdominal pain. She thought it was a urinary tract infection so she took trimethoprim-sulfamethoxazole that she had left over. She planned on going to her primary care physician today but then she developed headache and blurry vision so she came to the emergency department. The patient states she is otherwise healthy. Her family history is significant for a brother with sickle cell trait. On physical examination, there is mild abdominal tenderness, and the liver edge is felt 4 cm below the right costal margin. Labs are drawn as below: Hemoglobin: 7.0 g/dL Platelets: 149,000/mm^3 Reticulocyte count: 5.4% Lactate dehydrogenase: 3128 U/L Total bilirubin: 2.1 mg/dL Indirect bilirubin: 1.4 mg/dL Aspartate aminotransferase: 78 U/L Alanine aminotransferase: 64 U/L A peripheral smear shows polychromasia. A Doppler ultrasound of the liver shows decreased flow in the right hepatic vein. Magnetic resonance imaging of the brain is pending. Which of the following tests, if performed, would most likely identify the patient’s diagnosis?

• A. Flow cytometry (Correct Answer)
• B. Glucose-6-phosphate-dehydrogenase levels
• C. Anti-histone antibodies
• D. Bone marrow biopsy
• E. Hemoglobin electrophoresis

Hematopathology Explanation: ***Flow cytometry*** - The patient's symptoms (headache, blurry vision, dark urine, abdominal pain, hepatomegaly) along with laboratory findings of **hemolytic anemia** (low hemoglobin, elevated reticulocyte count, high LDH, elevated indirect bilirubin) and signs of **thrombosis** (decreased hepatic vein flow, neurological symptoms) are highly suggestive of **paroxysmal nocturnal hemoglobinuria (PNH)**. - **Flow cytometry** is the gold standard for diagnosing PNH by detecting the absence of **CD55** and **CD59** on red blood cells, granulocytes, and monocytes, indicating a deficiency in the **GPI anchor protein**. *Glucose-6-phosphate-dehydrogenase levels* - **G6PD deficiency** typically presents with hemolytic anemia triggered by **oxidant stressors** (like trimethoprim-sulfamethoxazole) but does not typically cause **thrombosis** or widespread organ involvement (e.g., hepatic vein thrombosis, neurological symptoms) as seen in this patient. - Measuring G6PD levels would be appropriate if G6PD deficiency was suspected, but the clinical picture points more strongly to PNH due to the thrombotic events. *Anti-histone antibodies* - **Anti-histone antibodies** are primarily associated with drug-induced **lupus erythematosus**, which can manifest with various systemic symptoms, but not typically with severe hemolytic anemia and thrombotic microangiopathy in this specific pattern. - While drug exposure is present (trimethoprim-sulfamethoxazole), the overall clinical and lab findings (especially the severe hemolytic picture and thrombosis) are not characteristic of drug-induced lupus in this context. *Bone marrow biopsy* - A **bone marrow biopsy** might show findings consistent with increased erythropoiesis due to hemolysis but is not a primary diagnostic test for PNH or its associated thrombotic complications. - While it could be part of an evaluation for underlying bone marrow disorders, it would not directly confirm a diagnosis of PNH, which requires specific surface marker detection. *Hemoglobin electrophoresis* - **Hemoglobin electrophoresis** is used to diagnose **hemoglobinopathies** such as **sickle cell disease** or **thalassemia**. The patient's brother has sickle cell trait, but the patient's symptoms, particularly the prominent hemolytic anemia and thrombotic events, are not typical of a hemoglobinopathy in this acute presentation. - While it could rule out a hemoglobinopathy, it wouldn't explain the full spectrum of symptoms, especially the thrombosis and the specific pattern of hemolysis (e.g., elevated LDH, indirect bilirubin).

Hematopathology US Medical PG Question 10: A 48-year-old man is being evaluated for an acquired defect of the myeloid stem cell line with a mutation in the PIG-A gene. His diagnosis was first suspected due to anemia and recurrent pink-tinged urine. Which of the markers will be negative in the flow cytometry test for his condition?

• A. CD18
• B. CD3
• C. CD19
• D. CD40L
• E. CD55 (Correct Answer)

Hematopathology Explanation: ***CD55*** - This patient presents with symptoms and genetic findings (PIG-A mutation) consistent with **Paroxysmal Nocturnal Hemoglobinuria (PNH)**. PNH is characterized by a defect in the synthesis of **GPI anchors**, which attach certain proteins, like CD55 (DAF) and CD59 (MIRL), to the cell surface. - In PNH, cells lacking GPI anchors, specifically **erythrocytes, granulocytes, and monocytes**, will show reduced or absent expression of CD55 and CD59 on flow cytometry, making CD55 a key diagnostic marker that will be **negative**. *CD18* - **CD18** is part of the **integrin family** and is expressed on **leukocytes**, playing a crucial role in cell adhesion and migration. It is not directly affected by the PIG-A gene mutation or the GPI anchor deficiency seen in PNH. - Its expression would typically be normal in PNH patients. *CD3* - **CD3** is a surface marker specific to **T lymphocytes**, involved in T-cell receptor signaling. PNH primarily affects myeloid stem cells and their descendants, leading to GPI anchor deficiency on cells like erythrocytes, granulocytes, and monocytes. - T-lymphocytes are generally not affected by the PIG-A mutation, so CD3 expression would be normal. *CD19* - **CD19** is a marker expressed on **B lymphocytes** and is involved in B-cell development and activation. The PIG-A mutation and subsequent GPI anchor deficiency primarily impact myeloid cells and, to a lesser extent, erythroid cells. - B-lymphocytes are not typically affected by the GPI-anchor deficiency; therefore, CD19 expression would be normal. *CD40L* - **CD40L (CD154)** is a protein expressed on activated **T lymphocytes** and plays a critical role in T-cell-dependent B-cell activation and antibody production. Like CD3, it relates to T-cell function and is not directly linked to the PIG-A mutation or GPI anchor deficiency in PNH. - Its expression would not be negative in this condition.

Hematopathology Flashcard 1 of 8

Question: _____ disorders are neoplastic proliferations of mature cells of myeloid lineage

Answer: Myeloproliferative

Hematopathology Flashcard 2 of 8

Question: Chronic myeloproliferative disorders (except CML) are associated with _____ mutations

Answer: V617F JAK2

Hematopathology Flashcard 3 of 8

Question: Acute leukemia is defined as a neoplastic proliferation of blasts _____% in the bone marrow

Answer: > 20

Hematopathology Flashcard 4 of 8

Question: Myelodysplastic syndromes rarely may progress to _____ leukemia

Answer: acute myeloid

Hematopathology Flashcard 5 of 8

Question: What are the associated tumors (2) that result from gain of function of the Bcl-2 oncogene?_____

Answer: follicular and diffuse large B-cell lymphomas

Hematopathology Flashcard 6 of 8

Question: What cancer has a higher incidence in patients with paroxysmal nocturnal hemoglobinuria? _____

Answer: Acute myeloid leukemia (AML) (specific)

Hematopathology Flashcard 7 of 8

Question: testicular lymphoma

Answer: mets from primary lymphoma

Extra Information: poor; aggressiveolder men

Hematopathology Flashcard 8 of 8

Question: What kinds of tissue samples can be used for karyotyping?

Answer: blood, bone marrow, amniotic fluid, placental tissue